Chemical characterization of pharmaceutical products, from the drug discovery phase to the final product stage, is an important requirement of new drug development. The instruments and methods used should be sensitive enough to detect all physiologically significant components or contaminants at physiologically significant levels. Current methods for these analyses involve expensive or time-consuming processes. The long-term objective of this project is to develop a commercially viable CNLSD detector initially targeted for use within the pharmaceutical industry. Short-term objectives are to develop a prototype CNLSD detector and to develop partnerships with major pharmaceutical companies such as Eli Lilly, Pfizer and Baxter Healthcare. The prototype will incorporate technology currently commercially available in the Nonvolatile Residue Monitor (NRM). The CNLSD detector will measure complex matrices at lower detection levels than existing instrumentation. The PIs have been working in parallel on technology with the potential to provide a reasonably priced, commercial system that has response for virtually any chemical compound with high sensitivity. PI JAK has extensive experience with CNLSD, HPLC methods and development. PI DBB has experience and capability for developing, manufacturing and marketing analytical instruments, including the NRM. The collaboration of PIs JAK and DBB provides the necessary expertise and resources to successfully complete this project. Phase I of this project includes designing and developing a prototype HPLC-CNLSD at PI DBB's facilities. The prototype will be evaluated at PI JAK's laboratory using a formalized testing protocol. An iterative design process will be used, addressing any design flaws and collaborating with pharmaceutical partners to incorporate their specific requests. Success of the project will result in chemical analysis methodologies that will improve the quality of the measurements obtained, while also reducing the costs for drug development and therefore the costs of pharmaceuticals to the consumer.